PDF(Pubmed)
Abstract：
UNASSIGNED: Manifestations of thyroid-associated ophthalmopathy (TAO) vary greatly. Few tools and indicators are available to assess TAO, restricting personalized diagnosis and treatment.
UNASSIGNED: To identify an aptamer targeting thyroid-stimulating hormone receptor (TSHR) and utilize this aptamer to evaluate clinical activity in patients with TAO.
UNASSIGNED: An aptamer targeting TSHR was developed by exponential enrichment and systematic evaluation of TSHR ligands. After truncation and optimization, the affinity, equilibrium dissociation constant, and serum stability of this aptamer were evaluated. The affinity of the TSHR-targeting aptamer to isolated fibrocytes was assessed, as was aptamer internalization by fibrocytes. The mechanism of binding was determined by molecular docking. The correlation between disease manifestations and the percentage of TSHR-positive cells was assessed by correlation analysis.
UNASSIGNED: The aptamer TSHR-21-42 was developed to bind to TSHR, with the equilibrium dissociation constant being 71.46 Kd. Isolated fibrocytes were shown to bind TSHR-21-42 through TSHR, with its affinity maintained at various temperatures and ion concentrations. TSHR-21-42 could compete with anti-TSHR antibody, both for binding site to TSHR and uptake by cells after binding. In addition, TSHR-21-42 could bind to leukocytes in peripheral blood, with this binding differing in patients with TAO and healthy control subjects. The percentage of TSHR-positive monocytes, as determined by binding of TSHR-21-42, correlated positively with clinical activity score in patients with TAO, indicating that TSHR-21-42 binding could assess the severity of TAO.
UNASSIGNED: This aptamer targeting TSHR may be used to objectively assess disease activity in patients with TAO, by evaluating the percentages of TSHR positive cells in peripheral blood.
UNASSIGNED: To identify an aptamer targeting thyroid-stimulating hormone receptor (TSHR) and utilize this aptamer to evaluate clinical activity in patients with TAO.
UNASSIGNED: An aptamer targeting TSHR was developed by exponential enrichment and systematic evaluation of TSHR ligands. After truncation and optimization, the affinity, equilibrium dissociation constant, and serum stability of this aptamer were evaluated. The affinity of the TSHR-targeting aptamer to isolated fibrocytes was assessed, as was aptamer internalization by fibrocytes. The mechanism of binding was determined by molecular docking. The correlation between disease manifestations and the percentage of TSHR-positive cells was assessed by correlation analysis.
UNASSIGNED: The aptamer TSHR-21-42 was developed to bind to TSHR, with the equilibrium dissociation constant being 71.46 Kd. Isolated fibrocytes were shown to bind TSHR-21-42 through TSHR, with its affinity maintained at various temperatures and ion concentrations. TSHR-21-42 could compete with anti-TSHR antibody, both for binding site to TSHR and uptake by cells after binding. In addition, TSHR-21-42 could bind to leukocytes in peripheral blood, with this binding differing in patients with TAO and healthy control subjects. The percentage of TSHR-positive monocytes, as determined by binding of TSHR-21-42, correlated positively with clinical activity score in patients with TAO, indicating that TSHR-21-42 binding could assess the severity of TAO.
UNASSIGNED: This aptamer targeting TSHR may be used to objectively assess disease activity in patients with TAO, by evaluating the percentages of TSHR positive cells in peripheral blood.
摘要：
■甲状腺相关眼病（TAO）的表现差异很大。很少有工具和指标可用于评估TAO，限制个性化诊断和治疗。
■为了鉴定靶向促甲状腺激素受体（TSHR）的适体，并利用该适体评估TAO患者的临床活性。
■通过指数富集和TSHR配体的系统评估开发了靶向TSHR的适体。截断和优化后，亲和力，平衡解离常数，并对该适体的血清稳定性进行了评价。评估了TSHR靶向适体对分离的纤维细胞的亲和力，适体通过纤维细胞内化也是如此。通过分子对接确定结合的机制。通过相关性分析评估疾病表现与TSHR阳性细胞百分比之间的相关性。
■开发了与TSHR结合的适体TSHR-21-42，平衡解离常数为71.46Kd。分离的纤维细胞显示通过TSHR结合TSHR-21-42，在各种温度和离子浓度下保持其亲和力。TSHR-21-42可以与抗TSHR抗体竞争，无论是与TSHR的结合位点，还是结合后细胞的摄取。此外,TSHR-21-42可与外周血白细胞结合,这种结合在TAO患者和健康对照受试者中不同。TSHR阳性单核细胞的百分比,通过TSHR-21-42的结合确定，与TAO患者的临床活动评分呈正相关，表明TSHR-21-42结合可以评估TAO的严重程度。
■这种靶向TSHR的适体可用于客观评估TAO患者的疾病活动，通过评估外周血中TSHR阳性细胞的百分比。
■为了鉴定靶向促甲状腺激素受体（TSHR）的适体，并利用该适体评估TAO患者的临床活性。
■通过指数富集和TSHR配体的系统评估开发了靶向TSHR的适体。截断和优化后，亲和力，平衡解离常数，并对该适体的血清稳定性进行了评价。评估了TSHR靶向适体对分离的纤维细胞的亲和力，适体通过纤维细胞内化也是如此。通过分子对接确定结合的机制。通过相关性分析评估疾病表现与TSHR阳性细胞百分比之间的相关性。
■开发了与TSHR结合的适体TSHR-21-42，平衡解离常数为71.46Kd。分离的纤维细胞显示通过TSHR结合TSHR-21-42，在各种温度和离子浓度下保持其亲和力。TSHR-21-42可以与抗TSHR抗体竞争，无论是与TSHR的结合位点，还是结合后细胞的摄取。此外,TSHR-21-42可与外周血白细胞结合,这种结合在TAO患者和健康对照受试者中不同。TSHR阳性单核细胞的百分比,通过TSHR-21-42的结合确定，与TAO患者的临床活动评分呈正相关，表明TSHR-21-42结合可以评估TAO的严重程度。
■这种靶向TSHR的适体可用于客观评估TAO患者的疾病活动，通过评估外周血中TSHR阳性细胞的百分比。
